Stavudine dosage reduction: Effect on symptomatic hyperlactataemia and lactic acidosis in patients at Dr George Mukhari Hospital, Pretoria

A range of studies have demonstrated that symptomatic hyperlactataemia and lactic acidosis are associated with antiretroviral combinations containing stavudine. Following a meta-analysis showing that lower doses of stavudine are safer and as effective, the World Health Organization (WHO) issued a statement that only a low dose of stavudine (30 mg) should be used. We performed a retrospective review of the records of 86 patients (aged 27 - 59 years) initiated on 30 mg or 40 mg stavudine-containing antiretroviral therapy regimens between 2004 and 2006 at the adult HIV clinic at Dr George Mukhari Hospital, Pretoria, South Africa. Our analysis demonstrated that stavudine dose reduction increased the odds of patients being more stable on treatment with fewer reported side-effects. Stavudine-containing regimens should be avoided in obese female patients. Low-dose stavudine (20 mg) may offer alternative solutions in poor or resource-limited settings, with a lower associated risk of toxicity and side-effects; however, virological non-inferiority to the first-line treatment option should be established

Scientific Letter: Stavudine dosage reduction: Effect on symptomatic hyperlactataemia and lactic acidosis in patients at Dr George Mukhari Hospital, Pretoria

Scientific Letter: No Abstrac

CASE REPORT: Disseminated fatal Talaromyces (Penicillium) marneffei infection in a returning HIV-infected traveller

We report a case of disseminated fatal Talaromyces (Penicillium) marneffei infection in an HIV-infected, antiretroviral treatmentexperienced South African woman who had travelled to mainland China. The 37-year-old woman was admitted to a private hospital in fulminant septic shock and died within 12 h of admission. Intracellular yeast-like bodies were observed on the peripheral blood smear. A serum cryptococcal antigen test was negative. Blood cultures flagged positive after 2 days; on direct microscopy, yeast-like bodies were observed and a thermally dimorphic fungus, confirmed as T. marneffei, was cultured after 5 days. The clinical features of HIV-associated disseminated penicilliosis overlap with those of tuberculosis and endemic deep fungal infections. In the southern African context, where systemic opportunistic fungal infections such as cryptococcosis are more common among HIV-infected patients with a CD4+ count of <100 cells/µL, this infection is not likely to be considered in the differential diagnosis unless a travel history is obtained

Functional Characterization of Cryptococcal Genes: Then and Now

Site-directed mutagenesis enables researchers to switch a gene of interest off for functional characterization of the gene. In the pathogenic yeasts, Cryptococcus neoformans and sister species C. deneoformans, this is almost exclusively achieved by introducing DNA into cells through either biolistic transformation or electroporation. The targeted gene is then disrupted by homologous recombination (HR) between the gene and the transforming DNA. Both techniques have downsides; biolistic transformation equipment is very expensive, limiting the use thereof to well-resourced laboratories, and HR occurs at extremely low frequencies in electroporated cryptococcal cells, making this method unappealing for gene targeting when not making use of additional modifications or methods to enhance HR in these cells. One approach to increase the frequency of HR in electroporated cryptococcal cells have recently been described. In this approach, CRISPR-Cas9 technology is utilized to form a double strand break in the targeted gene where after the occurrence of HR seems to be higher. The less expensive electroporation technique can therefore be used to deliver the CRISPR-Cas9 components into cells to disrupt a gene of interest, but only if the CRISPR components can be maintained for long enough in cells to enable their expression. Maintenance of episomal DNA occurs readily in C. deneoformans, but only under certain conditions in C. neoformans. In addition, CRISPR-Cas9 allows for gene complementation in order to fulfill Falkow’s molecular Koch’s postulates and adds other novel methods for studying genes as well, such as the addition of a fluorophore to an inactive Cas9 enzyme to highlight the location of a gene in a chromosome. These developments add less expensive alternatives to current methods, which could lead to more research on this yeast in developing countries where cryptococcal infections are more prevalent and researchers have access to more clinical isolates

The \u3ci\u3eCryptococcus neoformans\u3c/i\u3e Flc1 Homologue Controls Calcium Homeostasis and Confers Fungal Pathogenicity in the Infected Hosts

Cryptococcus neoformans, an opportunistic yeast pathogen, relies on a complex network of stress response pathways that allow for proliferation in the host. In Saccharomyces cerevisiae, stress responses are regulated by integral membrane proteins containing a transient receptor potential (TRP) domain, including the flavin carrier protein 1 (Flc1), which regulates calcium homeostasis and flavin transport. Here, we report that deletion of C. neoformans FLC1 results in cytosolic calcium elevation and increased nuclear content of calcineurin-dependent transcription factor Crz1, which is associated with an aberrant cell wall chitin overaccumulation observed in the flc1Δ mutant. Absence of Flc1 or inhibition of calcineurin with cyclosporine A prevents vacuolar fusion under conditions of combined osmotic and temperature stress, which is reversed in the flc1Δ mutant by the inhibition of TORC1 kinase with rapamycin. Flc1-deficient yeasts exhibit compromised vacuolar fusion under starvation conditions, including conditions that stimulate formation of carbohydrate capsule. Consequently, the flc1Δ mutant fails to proliferate under low nutrient conditions and displays a defect in capsule formation. Consistent with the previously uncharacterized role of Flc1 in vacuolar biogenesis, we find that Flc1 localizes to the vacuole. The flc1Δ mutant presents a survival defect in J774A.1 macrophage cell-line and profound virulence attenuation in both the Galleria mellonella and mouse pulmonary infection models, demonstrating that Flc1 is essential for pathogenicity. Thus, cryptococcal Flc1 functions in calcium homeostasis and links calcineurin and TOR signaling with vacuolar biogenesis to promote survival under conditions associated with vacuolar fusion required for this pathogen’s fitness and virulence

An African perspective on the genetic diversity of Toxoplasma gondii: A systematic review

The study of Toxoplasma gondii genotypes is beneficial for detecting strains linked to increased disease severity and uncovering the processes involved in the transmission and distribution of this zoonotic parasite. A systematic review of literature was conducted to investigate the present status of T. gondii genetic diversity in African countries and among host species on the continent. Data from the results in the included studies were sorted, reviewed and descriptively analysed using tables, graphs and maps. Results indicate that there is a relative amount of genetic diversity with a clear difference in the population structure between geographical regions and the propensity for unique and regional genotypes to be predominant in tropical rainforest biomes, near the equator. From a clinical perspective, connections between specific T. gondii genotypes and disease manifestations were found. Theories are outlined on the dissemination of African T. gondii genotypes to other continents. The overrepresentation of samples from one geographical area and dissimilar genotyping methodologies creates challenges when concluding on the genetic diversity of T. gondii in Africa. The need for uniform genotyping methods with a continent-wide sampling of an extensive host range involving humans, domestic animals and wildlife is emphasized

Medicinal plant cultivation for sustainable use and commercialisation of high-value crops

Many traditional healing systems are based on natural biological resources, and there is a general shift in most parts of the world towards natural medicine, with direct implications on the demand and supply of medicinal plants. This review highlights the economic importance of medicinal plants, their contribution to healthcare systems, and potential opportunities for rural economic development through cultivation.  A systematic literature review with specific search terms related to medicinal plants was used to collect scientific and non-scientific information from peer-reviewed literature and grey literature databases. The findings indicate that trade in medicinal plants is increasing, and although they are considered minor crops compared to major food crops, their value is among the highest in the list of traded plants globally. The trade also serves as a revenue source for many rural livelihoods, with women playing a significant role. Medicinal plants contribute to primary health care in many developing countries, and they are also an essential source of modern drug discovery. Cultivation of medicinal plants offers emerging rural farmers an opportunity to grow these plants as new and alternative crops, thus reducing unsustainable wild harvesting and competition with established commercial farmers who mostly focus on food crops. Furthermore, medicinal plant cultivation should be promoted as one of the options for local economic development and sustainability through job creation, the revival of the rural economy, and income generation for small businesses, such as the transport businesses, involved in the value chain. Land accessibility, financial resources, and direct market access for rural communities can elevate their contribution to the industry. Formalisation of the lower levels of the medicinal plant trade is also recommended. Significance:• Cultivation is a viable option for biodiversity conservation of medicinal plants and ensuring a goodquality supply of plant materials.• Cultivation of medicinal plants – a source of natural products used in product development – can contribute to job creation, income generation, and rural economies in developing countries.• This review underlines the importance of medicinal plants in product development, the contribution of the industry to economies of different countries, and the potential for cultivation

Transplant Unit, Division of General Surgery, Department of Surgery, Faculty of Health Sciences, University of Cape Town, South Africa

Organ and tissue donation depends on non-transplant clinicians to identify and timeously refer potential donors and to counsel families compassionately about the prognosis at end of life. Organ donation referral is often felt to be beyond the capacity of district-level hospital services. In this case series, we report on four referrals from a geographically remote, public sector district-level hospital, and review the identification, referral and consent process of potential donors after brain death, and also donors after circulatory death. For the one successfully consented donor we report on the donor work-up and management, and the outcome of the organ recovery and organ allocation process

Saartjie Baartman, Nelisiwe Xaba, and me: the politics of looking at South African bodies

Dance Artist/Choreographer Nelisiwe Xaba’s They Look at Me and That Is All They Think (2006) ‘refers to the story of Sara[tjie] Baartman […] the “Hottentot Venus”’ (2006. 9th Jomba! Contemporary dance experience 2006 programme, p. 7) who was taken from her homeland South Africa, and exhibited in Europe in the nineteenth century. After Baartman died in 1815, her remains were displayed in a museum in Paris until 1982. Xaba parallels the story of Baartman to her own experience of performing in Europe as a black South African woman. This article considers how They Look at Me and That Is All They Think exposes the politics surrounding the act of looking at a particular racial and gendered body in both the historical and contemporary context, and how the concept and articulation of the ‘superior’ European subject was dependent on the classification of Baartman, and other black Africans, as exotic others. In my practice-based research project How I Chased a Rainbow And Bruised My Knee (2007), which was a choreographic response to Xaba’s work, I theatricalize my identity as a white South African woman to make visible whiteness, its associated privilege, and how it is dependent on the representation of a particular type of blackness

Bikeshare on a University Campus: Lessons from a Pilot Project at the University of Pretoria

In 2018 the University of Pretoria implemented a bikeshare system as a pilot project on its campus to test its feasibility, and to help develop the capacity of City of Tshwane officials to implement future bicycle promotion schemes. Innovative aspects of the pilot included the inclusion of both electric and manual bicycles in a hybrid fleet, the development of a web-based booking and registration system, and the continuous GPS tracking of bicycles for security and data collection purposes. Pre- and post surveys and focus groups provided information on the demand for bikeshare, and how it was used. The paper reviews this evidence, concluding that there is a demonstrated role for bikeshare in certain niche markets in South African cities. Bikeshare’s biggest benefit is its potential to expand the mobility of current pedestrians, although it also demonstrated a modest ability to capture trips from car users and to support public transport as a first/last kilometer solution.Papers presented at the 38th International Southern African Transport Conference on "Disruptive transport technologies - is South and Southern Africa ready?" held at CSIR International Convention Centre, Pretoria, South Africa on 8th to 11th July 2019